Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6657103

Title:Human antibodies derived from immunized xenomice
Inventors:Kucherlapati, Raju; Darien, CT, USA
Jakobovits, Aya; Menlo Park, CA, USA
Klapholz, Sue; Stanford, CA, USA
Brenner, Daniel G.; San Mateo, CA, USA
Capon, Daniel J.; Hillsborough, CA, USA
Summary:This invention describes the production of fully human immunoglobulin specific for a desired antigen, via immunization of a non-human animal which cannot produce endogenous Ig but which produces human Ig. It has been shown that antibodies with fully human variable regions against a specific antigen can be prepared by administration of the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Also described are various subsequent manipulations which can be performed to obtain either antibodies per se or analogs thereof. Fully detailed is a method for producing a human IgM comprising a nonchimeric variable region, wherein the immunoglobulin is specific for a desired antigen. Also provided are methods of administration of the antigen, or an immunogenic portion thereof, to a transgenic mouse under conditions which stimulate an immune response such that the mouse produces B cells which in turn yield the specific immunoglobulin for the specific antigen. Further described are genomic properties of the transgenic mouse, which are characterized by inactivated endogenous immunoglobulin heavy chain loci in which all of the J segment genes are deleted to prevent rearrangement of the loci and to prevent formation of a transcript of a rearranged immunoglobulin heavy chain locus, and by concurrently inactivated endogenous immunoglobulin light chain loci in which genes are deleted to prevent rearrangement of the loci and to prevent formation of a transcript of a rearranged immunoglobulin light chain locus. Therapeutic applications are also provided. This invention represents a continuation of additional applications filed by the same assignee and inventors.
Abstract:Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6657103
Application Number:US1997000923138
Date Filed:04/09/1997
Date Published:02/12/2003
Assignee:Abgenix, Inc., Fremont, CA, USA


 
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